Dynamic modulation of HSV chromatin drives initiation of infection and provides targets for epigenetic therapies

Virology. 2015 May:479-480:555-61. doi: 10.1016/j.virol.2015.01.026. Epub 2015 Feb 18.

Abstract

Upon infection, the genomes of herpesviruses undergo a striking transition from a non-nucleosomal structure to a chromatin structure. The rapid assembly and modulation of nucleosomes during the initial stage of infection results in an overlay of complex regulation that requires interactions of a plethora of chromatin modulation components. For herpes simplex virus, the initial chromatin dynamic is dependent on viral and host cell transcription factors and coactivators that mediate the balance between heterochromatic suppression of the viral genome and the euchromatin transition that allows and promotes the expression of viral immediate early genes. Strikingly similar to lytic infection, in sensory neurons this dynamic transition between heterochromatin and euchromatin governs the establishment, maintenance, and reactivation from the latent state. Chromatin dynamics in both the lytic infection and latency-reactivation cycles provides opportunities to shift the balance using small molecule epigenetic modulators to suppress viral infection, shedding, and reactivation from latency.

Keywords: Chromatin; Demethylase; HCF-1; Herpes simplex virus; JMJD2; LSD1; Latency.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Chromatin / metabolism*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Viral*
  • Host-Pathogen Interactions
  • Simplexvirus / genetics
  • Simplexvirus / physiology*
  • Transcription Factors / metabolism
  • Virus Latency*
  • Virus Replication*

Substances

  • Chromatin
  • Transcription Factors